<p class="abstract"><strong>Background:</strong> Various orthopaedic conditions end up being painful, chronic and progressive, and are associated with persistent inflammation. The present study aimed to evaluate the efficacy and safety of an enzyme-bioflavonoid combination of trypsin-bromelain-rutoside in managing the chronic pain and swelling in out-patients with various orthopaedic conditions.</p><p class="abstract"><strong>Methods:</strong> The study was a prospective, observational study, conducted in 100 patients attending the orthopaedics department at a multi-speciality hospital located in Nashik, Maharashtra, India.  Verbal rating scales were used for grading the pain intensity and extent of swelling at baseline and on days 3 and 8, after being prescribed oral tablets of trypsin-bromelain-rutoside combination. Scores were analysed using paired t test. A 5-point Likert scale was used to evaluate patient- and investigator-reported global assessment of improvement in pain and swelling at days 3 and 8.<strong></strong></p><p class="abstract"><strong>Results:</strong> At baseline, 68 patients reported moderate-severe pain, while 74 patients had moderate swelling. The mean scores for pain and swelling showed statistically significant reduction at both day 3 (p&lt;0.0001) and day 8 (p&lt;0001). By day 8, 98 patients reported good-excellent improvement and the investigator reported good-excellent improvement in 97 patients. No adverse event was reported by any patient.</p><p class="abstract"><strong>Conclusions:</strong> The results indicate that this therapy led to significant improvement in the pain and swelling as early as day 3 and further improvement with continued therapy, and can, thus, provide a safe alternative in patients with various orthopaedic conditions and reduce the need for other analgesic and anti-inflammatory drugs.</p>